P2X4 and P2X7 are essential players in basal T cell activity and Ca <sup>2+</sup> signaling milliseconds after T cell activation
Valerie J. Brock, Insa M. A. Wolf, Marco Er-Lukowiak, Niels Christian Lory, Tobias Stähler, Lena-Marie Woelk, Hans‐Willi Mittrücker, Christa E. Müller, Friedrich Koch‐Nolte, Björn Rissiek, René Werner, Andreas H. Guse, Björn‐Philipp Diercks
Abstract
Initial T cell activation is triggered by the formation of highly dynamic, spatiotemporally restricted Ca 2+ microdomains. Purinergic signaling is known to be involved in Ca 2+ influx in T cells at later stages compared to the initial microdomain formation. Using a high-resolution Ca 2+ live-cell imaging system, we show that the two purinergic cation channels P2X4 and P2X7 not only are involved in the global Ca 2+ signals but also promote initial Ca 2+ microdomains tens of milliseconds after T cell stimulation. These Ca 2+ microdomains were significantly decreased in T cells from P2rx4 −/− and P2rx7 −/− mice or by pharmacological inhibition or blocking. Furthermore, we show a pannexin-1–dependent activation of P2X4 in the absence of T cell receptor/CD3 stimulation. Subsequently, upon T cell receptor/CD3 stimulation, ATP release is increased and autocrine activation of both P2X4 and P2X7 then amplifies initial Ca 2+ microdomains already in the first second of T cell activation.